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We have shown that IFN\u2010\u03b3 production can be induced among human natural killer (NK) cells by coculture with <jats:italic>Plasmodium falciparum<\/jats:italic> infected erythrocytes, but the importance of this response is unclear. To further explore the role of NK cells during malaria infection, we have characterized the NK\u2010cell response of C57BL\/6 mice during lethal (<jats:italic>Py<\/jats:italic>YM) or nonlethal (<jats:italic>Py<\/jats:italic>17XNL) <jats:italic>P. yoelii<\/jats:italic> infection. Ex vivo flow cytometry revealed that NK cells are activated within 24 h of <jats:italic>Py<\/jats:italic>17XNL blood\u2010stage infection, expressing CD25 and producing IFN\u2010\u03b3; this response was blunted and delayed during <jats:italic>Py<\/jats:italic>YM infection. CD25 expression and IFN\u2010\u03b3 production were highly correlated, suggesting a causal relationship between the two responses. Subsequent in vitro experiments revealed that IL\u201018 signaling is essential for induction of CD25 and synergizes with IL\u201012 to enhance CD25 expression on splenic NK cells. In accordance with this, <jats:italic>Py<\/jats:italic>17XNL\u2010infected erythrocytes induced NK\u2010cell CD25 expression and IFN\u2010\u03b3 production in a manner that is completely IL\u201018\u2010 and partially IL\u201012\u2010dependent, and IFN\u2010\u03b3 production is enhanced by IL\u20102. These data suggest that IL\u20102 signaling via CD25 amplifies IL\u201018\u2010 and IL\u201012\u2010mediated NK\u2010cell activation during malaria infection.<\/jats:p>","DOI":"10.1002\/eji.201546018","type":"journal-article","created":{"date-parts":[[2015,9,30]],"date-time":"2015-09-30T09:07:21Z","timestamp":1443604041000},"page":"3431-3440","source":"Crossref","is-referenced-by-count":40,"title":["IL\u201018\u2010induced expression of high\u2010affinity IL\u20102R on murine NK cells is essential for NK\u2010cell IFN\u2010\u03b3 production during murine <i>Plasmodium yoelii<\/i> infection"],"prefix":"10.1002","volume":"45","author":[{"given":"Kerstin A.","family":"Stegmann","sequence":"first","affiliation":[{"name":"Faculty of Infectious and Tropical Diseases Department of Immunology and Infection London School of Hygiene and Tropical Medicine  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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